Ageing and the immune system Flashcards
what age does immune decline usually occur?
~60-70 yrs
what type of immune response decreases with age?
especially in T cell and B cell response
Decrease in response to vaccine
what antibody is present in breast milk?
IgA
what is senescence?
Biological aging
- is the gradual deterioration of functional characteristics
what is immunosenescence?
Gradual deterioration of immune system function
- reduced ability to fight infection
- reduced vaccine efficacy
- reduced tumour clearance
why does age effect immune response?
The aged immune system is less efficient at recognising and limiting infections
- increased incidence of infectious disease
- increased severity of infectious disease
Mechanical barriers weaken- less protective
what is IPD?
invasive pneumococcal disease
what is CAP?
community acquired pneumonia
where are the covid deaths increasing?
with age
deaths concentrated in older individuals
who is at greater risk of influenza?
Older adults at greater risk for severe influenza infection or complications of influenza
what are the features of Shinges (Herpes zoster) infection?
- reactivation of varicella zoster virus
- presenst as rash with acute pain, the rash follows the nerve path
- Complications include postherpetic neuralgia, vision loss, hearing loss, pneumonia, secondary bacterial infection
what is the efficacy of the shingles vaccine with age?
50-59 yrs= 70%
60-69 yrs= 64%
70-79 yrs= 41%
80+ yrs = 18% (no longer funded)
what is oligoclonal?
Derived from a few clones
what is monoclonal?
derived from one clone
what is polyclonal?
derived from many clones
what is the normal immune response?
polyclonal
what drives immunosenescence?
Reduced diversity of adaptive immune cells
- reduced T cell diversity
- reduced B cell diversity
- Due to reduced proportion of naive cells
- Oligo-clonal expansion of memory cells
why does the proportion of naive cells decrease with age?
the amount of precursor memory cells increases
why does T cell function decrease with age?
Decreased number of naive T cells in older age
- Progressive decrease in thymic output (thymic involution)
- Number of T cells remains constant (existing naive cell longlived)
how does the thymus change with age?
Increases in fat content
decreases in size- fewer T cells coming from the thymus
what us memory inflation in the immune system?
Accumulation of CD8 T cells with limited TCR repertoire (memory T cells)
why does T cell function decrease with an accumulation of memory T cells?
Increased proportion of memory T cells
- Accumulation of “virtual memory” CD8 T cells- cells that have a memory phenotype but are antigen-naive and conventional memory T cells
- Reduced functionality of virtual memory and conventional memory T cell subsets
what causes reduced function of mature B cells with age?
Inefficient generation of memory B cells
what causes impaired B cell development in age?
- decreased numbers of early B cell progenitors
- decreased expression of gene s important for B cell development
what causes decreased B cell function in the aged?
-Reduced function of mature B cells
-Impaired B cell development
-Alteration in the size and composition of the B cell repertorie (the number of different BCR expressed by an individual)
what are the outcomes of decreased B cells function?
Heightened susceptibility to infection, decreased antibody responses to vaccination, increase in the incidence of autoimmune disorders
what is the SLC in B cells?
surrogate light chain, important for B cell development to signal productive rearrangement of the heavy chain
what are ABCs?
Age-associated B cells
what are the features of Age Associated B cells?
- they rely on TLR7 or TLR9 signals for formation and activation- they don’t respond to BCR signaling alone.
- increased in autoimmune/autoinflammatory disease
- enriched for autoantibody specificities
what is the mechanism for inflammaging?
Heterogeneous exogenous and endogenous danger stimuli interact with a limited repetoir of sensors expressed on the cell surface and in the cytoplasm.
These result in a limited number of inflammatory responses.
With age, the pro-inflammatory output increase and becomes detrimental.
